| What is Down Syndrome Screening? |
What is Down Syndrome?
What is nuchal translucency, the AFP test, triple screen, quad screen?
What does Advanced Maternal Age mean?
The area of testing for Down Syndrome is one of the most active areas of research in Perinatology. This has become quite a complicated and frustrating area for patients. In addition, with the increasing number of women delaying childbearing it is also becoming even more important. AMA is defined as greater than 35 years old. This page reviews Down Syndrome: alpha-fetoprotein (AFP), triple quad screen, amniocentesis. Everything you need to know.
Down Syndrome, or Trisomy 21, is one of the most common chromosome disorders. In Trisomy 21, a fetus gets three copies of chromosome 21, two from his mother, one from his father. Normally, a fetus should only get one copy of this chromosome from each of his parents. Therefore fetuses have an extra chromosome in this chromosome disorder. the other chromosome disorders tend to be much more severe, even lethal for the fetus. Examples of these chromosome disorders are Trisomy 18 and Trisomy 13.
Advanced maternal age (AMA) is the most important risk factor for chromosome disorders. However, please note that 82% of babies with Trisomy 21 are born to women less than 35 years.
What is the risk of being AMA?
Age at Term: Risk of Down Syndrome: Risk of any Chromosome Disorder:
20 1: 1480 1: 525
35 1: 353 1: 178
40 1: 85 1: 62
45 1: 35 1: 18
The first key to understanding testing for Trisomy 21 is understanding the two basic types of tests:
1. Screening tests. These tests modify a woman's risk for having a fetus with Down Syndrome. They only offer a risk assessment. The most basic screen is advanced maternal age. If we only use age over 35 years, however, we will only detect 30% of cases of Down Syndrome. In the mid 1980's the AFP was introduced. Today most centers perform a triple or quad screen in the midtrimester, which includes an AFP. More recently, screening has moved into the first trimester with nuchal translucency testing.
2. Diagnostic tests. These tests are invasive, but they say with certainty if a fetus is affected or not. The two most common tests are chorionic villous sampling and amniocentesis. They are diagnostic because they actually obtain a karyotype of the fetus, or the complement of chromosomes. Although diagnostic in nature, they come with a risk of pregnancy loss.
SCREENING Tests for Chromosome Disorders:
Nuchal translucency testing:
In the last several years nuchal translucency testing has become widespread. This screen involves a risk assessment based upon four factors: age, one ultrasound measurement (nuchal translucency), and two serum markers (PAPP-A and beta-hCG). Together these test detect approximately 85% of fetuses with Down Syndrome, at a 5% false positive rate. This means if we examined 100 fetuses with Trisomy 21 we would detect 85. If examining 100 normal fetuses, 5 would fall into the abnormal result category. This false positive rate allows for the optimal number of fetuses with Down Syndrome to be detected. Nuchal translucency testing is quickly becoming the most popular method of screening for Trisomy 21, especially in women of advanced maternal age.
Nuchal translucency is an earlier risk assessment, performed at 11-14 weeks. It also is very sensitive. Earlier risk assessment allows for earlier diagnostic testing. In addition, there are other maternal and fetal conditions that can be diagnosed during this screening process. This includes multiple pregnancies and other major fetal defects. The findings on first trimester is an area being actively researched. See www.AskAnOB.com/nuchaltranslucency for additional information regarding this test.
Second Trimester Serum Screening/ AFP:
Typically called the AFP, triple screen or quad screen. This screen is a blood test that assays different markers that have a characteristic pattern in fetuses with major chromosomal disorders like Down Syndrome. This blood test is done between 15 and 20 weeks gestation. An AFP or triple screen picks up about 65% of fetuses with Down Syndrome. A quad screen detects about 80% when performed alone. The false positive rate of these tests is highly dependent upon maternal age. A woman over 35, and especially over 40, is more likely to have an abnormal test result, even with a normal fetus. This is one of the major disadvantages, especially in this high risk population. The AFP also screens for many other birth defects, such as neural tube defects. Finally, if a triple or quad screen is abnormal, even with normal chromosomes, this offers a red flag for future pregnancy complications. This includes: placental issues, growth restriction of the fetus, early delivery, blood pressure disorders of pregnancy and even stillbirth. For this reason, the AFP is valuable in predicting patients that should be watched very closely for these complications in the later pregnancy. Therefore even women who have diagnositic testing, should consider AFP.
Ultrasound and Down Syndrome:
When we perform our ultrasound at approximately 18 weeks, we look for many solid and soft markers for Down Syndrome. The problem is there is no finding all fetuses with Down Syndrome have that normal fetuses do not, and vice versa. In fact, 50% of fetuses with Down Syndrome will have no abnormal findings at all. Often when we know a fetus has Down Syndrome because a karyotype has already been performed, we still are unable to find any abnormal findings on ultrasound. Therefore, when I have a couple say "we won't worry as long as everything looks normal" I have to caution them that this is a false reassurance. Ultrasound simply isn't a good way to diagnose Down Syndrome.
DIAGNOSTIC TESTS for CHROMOSOME DISORDERS:
Chorionic Villous Sampling:
CVS is in essence a placental biopsy. Because this test results in a karyotype of the fetus, it is diagnostic. If a vaginal approach is used, it feels like a long Pap Smear to the patient. A catheter is placed through the cervix, to the tip of the placenta where a biopsy is obtained. Because both the fetus and the placenta develop from the fertilized egg, the placenta represents the fetal karyotype. The advantage of CVS includes the very early timing of the test: 9 to 13 weeks. The major disadvantage is a pregnancy loss rate that appears somewhat more than an amniocentesis, about 1%. In addition, it is much riskier if performed earlier than 9 weeks or after 13.
Amniocentesis Pros and Cons:
During an amniocentesis, your doctor uses a very thin needle to go through the abdominal wall, through the uterus and into the amniotic sac. About 20 mL of amniotic fluid is collected. The amniotic fluid is fetal urine, and contains many fetal cells. Most women state it is uncomfortable, but would not describe the procedure as painful. A genetic amniocentesis can be performed between 15 and 22 weeks. Results can take two weeks to get back. An amniocentesis is diagnostic. However, it also carries a pregnancy loss rate (See Recent Advances--Amniocentesis). Suffice it to say, this risk is somewhat less than 0.5%. Losses occur because of rupture of membranes, preterm labor, infection and bleeding. Rarely fetal injury occurs.
So after all this, I am sure your next question is: "So what test is right for me?". This is highly individualized to the specific desires of the couple. You must weigh the downsides of screening, nuchal translucency testing and alpha-fetoprotein, AFP, versus CVS or amniocentesis pros and cons, and decide which you are more comfortable with. If you would like to avoid an invasive procedure, and can accept a small risk the baby will have Down Syndrome, you should start with nuchal translucency testing and AFP testing. Using this approach we have been able to drastically reduce the number of invasive procedures we perform. If on the other hand you want absolute certainty and accept a small risk to the pregnancy, then you should opt for an invasive procedure.
This is a great area to utilize our MD Interactive Services, www.AskAnOB.com/questions so that you can get answers uniquely tailored to your pregnancy. See links below.
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| Schematic of an Amniocentesis |
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The schematic to the left depicts an amniocentesis. The skin is cleansed with antibiotic soap. Under ultrasound guidance the doctor inserts the needle all the way to the bag of water surrounding the baby. Then the doctor removes about 20 mL of fluid. The cells are collected from the fluid, and grown in culture. Then further testing, such as karyotype analysis, can be performed.
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